Cytokinetic factors in drug resistance of Lewis lung carcinoma: comparison of cells freshly isolated from tumours with cells from exponential and plateau-phase cultures

The mechanisms by which tumor cells resist the action of multiple anticancer drugs, often with widely different chemical structures, have been pursued for more than 30 years. The identification of P-glycoprotein (P-gp), a drug efflux transporter protein with affinity for multiple therapeutic drugs, provided an important potential mechanism and further work, which identified other members of ATP-binding cassette (ABC) family that act as drug transporters. Several observations, including results of clinical trials with pharmacological inhibitors of P-gp, have suggested that mechanisms other than efflux transporters should be considered as contributors to resistance, and in this review mechanisms of anticancer drug resistance are considered more broadly. Cells in human tumors exist is a state of continuous turnover, allowing ongoing selection and "survival of the fittest." Tumor cells die not only as a consequence of drug therapy but also by apoptosis induced by their microenvironment. Cell death can be mediated by host immune mechanisms and by nonimmune cells acting on so-called death receptors. The tumor cell proliferation rate is also important because it controls tumor regeneration. Resistance to therapy might therefore be considered to arise from a reduction of several distinct cell death mechanisms, as well as from an increased ability to regenerate. This review provides a perspective on these mechanisms, together with brief descriptions of some of the methods that can be used to investigate them in a clinical situation.

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Cytokinetic Resistance of Malignant Glioma Cells: Antineoplastic Agents During Maintenance Therapy

Hiraga¹,

Arita²,

Ohnishi³

et al. 1991

Biological Aspects of Brain Tumors

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Cytokinetic factors in drug resistance of Lewis lung carcinoma: comparison of cells freshly isolated from tumours with cells from exponential and plateau-phase cultures

Cited by 12 publications

References 12 publications

Acridine-based Anticancer Drugs

Acridine-based Anticancer Drugs

Classical and Targeted Anticancer Drugs: An Appraisal of Mechanisms of Multidrug Resistance

Cytokinetic Resistance of Malignant Glioma Cells: Antineoplastic Agents During Maintenance Therapy

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